Vacuum assisted percutaneous appliance

ABSTRACT

A device for reducing agent penetration at an insertion site is provided that has a porous inner sleeve fluidly connected to a conduit. A vacuum or hydrodynamic source is fluidly connected to the conduit. The device is stabilized by fibroblast in-growth and inhibits bacterial colonization. A device is also provided that has a conduit having a bore and an outer conduit surface. The outer conduit surface is optionally nanotextured to promote fibroblast adhesion and limit bacterial residency. A sleeve is provided in fluid communication with the bore of the conduit, and is formed from materials characterized by a pore matrix through which vacuum or hydrodynamic draw is achieved in a process to promote stabilization and reducing bacterial colonization by draw fluid from an area around the surrounding the site of the device. The sleeve optionally has a distal nanotextured surface.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority of U.S. Provisional Patent ApplicationSer. No. 61/307,166 filed Feb. 23, 2010; Ser. No. 61/406,814 filed Oct.26, 2010; and Ser. No. 61/419,491 filed Dec. 3, 2010, the contents ofwhich are incorporated herein by reference.

FIELD OF THE INVENTION

The invention relates in general to percutaneous access and inparticular to processes and devices for preventing infection at the siteof percutaneous access. More specifically, the invention providesprocesses and devices for preventing internalization of bacteria, otherinfectious agents, or other unwanted materials from entering the accesspoint for a catheter, Steinman pin, Kirschner wires, or otherpercutaneous instruments.

BACKGROUND OF THE INVENTION

Intravenous catheters act as an attachment point for microorganisms,leading to biofilm formation and infection at the site of insertion oralong the surface of the device.

Infection of the catheter hub and catheter-related bloodstreaminfections are major complications for patients with indwellingcatheters (e.g., Safdar and Maki, Intensive Care Med. 2004 January;30(1):62-7; Saint et al., Infect Control Hosp Epidemiol. 2000 June;21(6):375-80).

Prior attempts at controlling catheter-related infection are directed tosterilization techniques such as by topical or fluidic antibacterialsapplied to the insertion site or integrated into the catheter itself.The antimicrobial activity of ethyl alcohol (ethanol) as well as otheralcohols is well known. Isopropyl alcohol at a concentration of 60-70%is widely used as an antimicrobial agent for sanitization of surfacesand skin. A concentration of 10% ethyl alcohol inhibits the growth ofmost microorganisms, while concentrations of 40% and higher aregenerally considered bactericidal (Sissons et al., Archives of OralBiology, Vol. 41, 1, JN 1996; 27-34).

Catheterization can be kept in place for as little as a few seconds fordrainage or delivery. It is increasingly common, however, forpercutaneous access such as peripherally inserted central catheters(PICC), skeletal guide wires, cardiac assist device lines, or otherinstruments to be kept in place for weeks or months. The increased timein which such devices are maintained across the skin increases thelikelihood of instrument related infection.

Thus, there exists a need for processes and devices to prevent or reducethe likelihood of infection related to percutaneous instruments.

SUMMARY OF THE INVENTION

A device for reducing agent penetration at an insertion site is providedthat includes a porous inner sleeve fluidly connected to a conduit. Avacuum or hydrodynamic source is fluidly connected to the conduit tocreate a fluid draw from the subject tissue through the inner sleeve tothe conduit. The conduit is readily formed to have a bore and an outerconduit surface, the outer conduit surface being optionallynanotextured. The conduit bore is adapted to accommodate a medicalappliance. The sleeve in fluid communication with the conduit is readilyformed of materials characterized by a pore matrix through which vacuumor hydrodynamic draw is achieved without collapse under the vacuum orhydrodynamic draw conditions.

A process for stabilizing an implanted device at a percutaneousinsertion site in subject tissue includes inserting the aforementioneddevice subcutaneously and drawing vacuum against the subject tissue atthe insertion site through the sleeve and the conduit or fluid from theinsertion site through said conduit to draw fibroblasts into and ontosaid sleeve to stabilize the implanted device.

A kit for reducing agent penetration at a percutaneous insertion site insubject tissue is provided that includes a gasket connecting to apercutaneous access device and a bandage attached to the gasket to forma pressure-tight seal around the insertion site. A conduit associatedwith the percutaneous access device is in fluid communication with thebandage and the subject tissue surrounding the insertion site. A vacuumor hydrodynamic draw against the conduit serves to reduce agentpenetration at the percutaneous insertion site in the subject tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of an inventive device with therelative dimensions of aspects exaggerated for visual clarity;

FIG. 2 is a cross-sectional view of an inventive device with relativedimensions of aspects exaggerated for visual clarity depicting an outersleeve covering an inner sleeve for protection during skin penetration;

FIG. 3 is a cross-sectional view of an inventive device with relativedimensions of aspects exaggerated for visual clarity depicting a skinsurface terminating outer sleeve;

FIG. 4 is a perspective view of an inventive device employed with abandage providing a pressure seal to the outer surface of the skin;

FIG. 5 is a perspective view of an inventive device with relativedimensions of aspect exaggerated for visual clarity with an expandableouter sleeve;

FIG. 6 is a cross-sectional view of the relative dimensions of aspectsexaggerated for visual clarity depicting a pressure seal formed againstthe outer surface of the skin with resort to a gasket and a bandage;

FIG. 7A is a cross-sectional view of an inventive device with relativedimensions of aspect exaggerated for visual clarity depicting a siliconcollar and a plastic base forming a slidable pressure-tight seal againstthe outer surface of the skin;

FIG. 7B is a cross-sectional view of an inventive device with relativedimensions of aspect exaggerated for visual clarity depicting a siliconcollar and a plastic base forming a slidable pressure-tight seal againstthe outer surface of the skin;

FIG. 8A is a perspective cross-sectional view of percutaneous componentsof inventive device with relative dimensions of aspect exaggerated forvisual clarity depicting a flanged inner sleeve and an optionalopen-celled, implant compatible velour cuff;

FIG. 8B is an exploded view of FIG. 8A; and

FIG. 9 is a partial cutaway view of a flanged inventive device withrelative dimensions of aspect exaggerated for visual clarity.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following description of the preferred embodiment(s) is merelyexemplary in nature and is in no way intended to limit the scope of theinvention, its application, or uses, which may, of course, vary. Theinvention is described with relation to the non-limiting definitions andterminology included herein. These definitions and terminology are notdesigned to function as a limitation on the scope or practice of theinvention but are presented for illustrative and descriptive purposesonly. The inventive devices are disclosed herein in general with respectto a catheter, but this is not meant to be a limitation on theinvention. Any tube, instrument, wire, material or assembly thatpenetrates the skin of a subject is similarly operable for use with theinventive device or integral therewith.

The invention has utility as a device to reduce the likelihood ofpercutaneous instrument related infection.

An inventive device is intended for use with a percutaneous instrument.Any instrument that is intended to traverse the skin is operable withthe inventive device. The device is optionally used with a percutaneousaccess device illustratively a PICC, cannula, or other catheter, or pinillustratively a Steinman pin, Kirschner wires, and other devices orinstruments that penetrate the skin. It is appreciated that the deviceis similarly operable with bladder or other catheterization instrument.

The inventive devices decrease or prevent penetration or complicationsdue to the presence of an agent. As used herein an “agent” isillustratively: an infectious agent such as bacteria, virus, fungus,other organism; or foreign material. Illustrative examples of foreignmaterial include: bandage; soil; water, saliva, urine, or other fluid;feces; chemicals; or other matter known in the art. Illustrativeexamples of infectious agents that are prevented from penetrating orproduce complications include P. aeruginosa, E. cloacae; E. faecalis; C.albicans; K. pneumonia; E. coli; S. aureus; or other infectious agents.

An inventive device is optionally used on the epidermis of a subject. Asused herein, the term “subject” refers to a human or non-human animal,optionally a mammal including a human, non-primate such as cows, pigs,horses, goats, sheep, cats, dogs, avian species and rodents; and anon-human primate such as monkeys, chimpanzees, and apes; and a human,also denoted specifically as a “human subject”.

An inventive device illustratively operates by providing a force tocounteract fluid collection or flow along a percutaneousinstrument-tissue interface. It is common for fluid to develop in thespace surrounding a percutaneous instrument often beginning immediatelyafter insertion. The presence of this fluid allows migration, flow, orother penetration of agents normally excluded by the intact skin toareas below the skin. The penetration by these agents may lead todevelopment of infectious disease, inflammation at the site ofinsertion, or other unwanted complications.

As used herein, an “insertion site” is defined as an intentionalinterruption of skin or other tissue for the placement of a medicalappliance.

A force is illustratively a vacuum. A vacuum illustratively preventsfluid from moving along an interface between tissue and the embeddedcatheter or other instrument. The negative pressure of the vacuum allowsthe natural pressures of biological material or other atmosphericpressure to move unwanted material away from the areas at or below thesite of insertion.

An inventive device includes one or more sleeves. A sleeve is optionallyan inner sleeve or an outer sleeve. As used herein, the terms “inner”and “outer” are relative terms in terms of encompassing relativedimensions and should not be construed contextually as to positioningrelative to the epidermis. An inner sleeve is optionally made of aporous material or scaffold that is optionally penetrated by fluids orgasses. A scaffold is optionally a tissue scaffold that allows orpromotes attachment of cells, illustratively, fibroblasts to the surfaceof an inner sleeve. An inner sleeve is optionally treated. An innersleeve treatment illustratively includes compounds or surface texturesthat promote attachment of fibroblasts or other cellular material.Optionally, the inner sleeve is made of a woven material. A wovenmaterial is optionally penetratable by cells, fluids, gas, or othermaterials.

It is appreciated that an inner sleeve is optionally the only sleevepresent in the device. An inner sleeve is optionally a porous scaffoldthat is suitable for moving fluid or gas through the sleeve away fromthe surrounding environment. Materials operable for use as an innersleeve illustratively include: collagen, PEBAX, nylons, polypropylenes,polyurethanes, polyethylenes (HDPE, UHWPE, LDPE, or any blend of theaforementioned polyethylenes), PET, NiTi, MYLAR, Nickel Titanium Alloy,other polymers such as other thermoplastic polymers, fabrics, siliconessuch as silicone rubber, latex, glass, or other materials known in theart. It is appreciated that polymeric materials with a gradient ofcross-linking density through the material afford certain advantageswith respect to promoting vacuum or hydrodynamic draw and fibroblastinfiltration. By way of example, a polymer having a greater rigidityproximal to the central axis of the device relative to the distalsurface inhibits pressure differential induced collapse. In someembodiments, an inner sleeve is made from chemically inert material. Insome embodiments, the porous scaffold is in direct contact with the skinof the subject or traverses the skin of the subject. In some embodimentsan inner sleeve is textured or woven in such a way so as to provideattachment sites for fibroblasts. A texture is optionally a nanotexture.Illustrative nanotextures have pore sizes that are uniformly less than500 nanometers to provide an anchor point for a fibroblast pseudopodextension, while having dimensions that disfavor bacterial colonization.A nanotextured surface as used herein has features indentations of from50 to 500 nanometer median dimension. In some embodiments, theindentations have a median dimension of between 100 and 300 nanometers.

In some embodiments, a texture is in the form of a scaffold. A scaffoldis illustratively formed of gold. A gold scaffold is optionally formedby making a sleeve from a gold/silver alloy that is dipped in an acidsuch as a mineral acid which selectively dissolves the silver leaving agold structure with appropriate porosity. Alternatively, a scaffold isformed from an acid etchable, biocompatible nanocrystal such as silveror silica is dispersed in a polymer melt such as polycarbonate and aneck either formed directly therefrom, or the nanocrystal-doped polymeris coated onto a neck substrate. Through subjecting thenanocrystal-doped polymer to an acid or base solution, depending on thesolubility of the nanocrystal, voids are formed in the polymerreflective of the original nanocrystal dopant. For instance, silver isreadily dissolved in 6 N hydrochloric acid while silica is dissolved inconcentrated hydrofluoric acid. Dissolution in the presence ofsonication is appreciated to facilitate the process. Nanocrystal loadingof 1 to 10 percent by weight, depending on the specific nanocrystaldimensions, is sufficient to achieve the desired uniformity and densityof pores. Other porous surfaces and methods of manufacture areillustrated in U.S. Pat. No. 7,704,225 and references cited therein,each of which are incorporated herein by reference in their entirety.

It is appreciated that an inner sleeve is optionally coated orimpregnated with a first compound. Coating or impregnating optionallyprovides lubrication so as to ease insertion of the instrument into theskin. A compound optionally: is antibacterial such as those described inWO 2008/060380, the contents of which are incorporated herein byreference; resist or promote cellular adhesion; are anticoagulants orprocoagulants; or other desirable compound.

A compound optionally includes factors operable to selectively promotefibroblast growth and/or decrease attachment of bacteria or othercontaminants. A compound optionally promotes growth of cells such asfibroblasts. A coating optionally includes the compound fibroblastgrowth factor (FBF). Optionally, FBF is used in a coating along withinsulin and/or dexamethasone. The presence of dexamethasone and/orinsulin will promote multiple layer growth of fibroblasts on the surfaceof or within the pores of a sleeve.

Coating substances illustratively include cell growth scaffoldingmatrices as detailed in U.S. Pat. Nos. 5,874,500; 6,056,970; and6,656,496; and Norman et al. Tissue Eng. 3/2005, 11(3-4) pp. 375-386,each of which is incorporated herein by reference. An exemplary coatingis a tissue scaffolding, poly-p xylylene, parylene and chemical modifiedversions of such coatings to enhance post-insertion stabilization.Chemical modifications illustratively include bonding of fibronectin andother molecules implicated in the healing process. While tissuescaffolding and polymers are readily applied by painting, dip coatingand spraying, it is also appreciated that polymeric coating are alsoreadily applied by gas phase deposition techniques such as chemicalvapor deposition (CVD). A coating is optionally porous in order toenhance capillary draw. In some embodiments a coating is biodegradable.A coating optionally has pores typically of an average size of between10 and 500 microns, optionally, of an average size of between 30 and 50microns.

An inventive device optionally includes an outer sleeve. An outer sleevefunctions to segregate or deliver vacuum draw pressure to an innersleeve. The outer sleeve optionally circumferentially and longitudinallycovers an inner sleeve. This configuration optionally shields the innersleeve from epidermal bacterial or other agents upon insertion.

An outer sleeve is optionally tapered at one or both ends. Tapering at adistal end (the end nearest the internal end of the catheter during use)provides improved insertion of the instrument into the skin of asubject. A taper may form a smooth interaction with the catheter at theouter sleeve distal end or a ridge is optionally present at or near thesite of device interaction with the catheter.

An outer sleeve is optionally made of any material suitable for use witha percutaneous instrument. Illustrative materials operable for an outersleeve include such materials that have a memory or are self-expanding.Materials operable for use as an outer sleeve illustratively include:PEBAX, nylons, polyurethanes, polyethylenes (HDPE, UHWPE, LDPE, or anyblend of the aforementioned polyethylenes), PET, NiTi, MYLAR, NickelTitanium Alloy, other polymers such as other thermoplastic polymers,fabrics, silicones such as silicone rubber, latex, glass, or othermaterials known in the art. An outer sleeve optionally includes or isformed of a scaffold. An outer sleeve scaffold is optionally made of thesame or different material as an inner sleeve scaffold. Scaffoldsoperable for an inner sleeve are similarly operable for an outer sleeve.

An outer sleeve is optionally expandable. An expandable outer sleeve isoptionally by stretch of the material, unfolding of the materialillustratively like of an accordion or other mechanism, or material thatwill provide expandability or compressibility to the outer sleeve.

It is appreciated that an outer sleeve is optionally coated orimpregnated with a second compound. A second compound is optionally thesame as a first compound. Coating or impregnation optionally provideslubrication so as to ease insertion of the instrument into the skin. Acompound optionally: is an antibacterial coating or impregnated materialsuch as those described in WO 2008/060380, the contents of which areincorporated herein by reference compounds to resist or promote cellularadhesion; anticoagulants or procoagulants; or other desirable compound.

In some embodiments, an outer sleeve is textured. A texture isoptionally formed of a tissue scaffold. A texture on an outer or innersleeve optionally has pore sizes, ridges, depressions, indentations, orother texture that is uniform or non-uniform. A texture is optionally ofa depth less than 500 nanometers to provide an anchor point for afibroblast pseudopod extension, while having dimensions that disfavorbacterial colonization. A nanotextured surface as used herein has auniform distribution of 50 to 500 nanometer median dimensionindentations. In some embodiments, the indentations have a mediandimension of between 100 and 300 nanometers.

In some embodiments an outer sleeve surrounds an inner sleeve. The outersleeve and inner sleeve are optionally formed from a unitary piece ofmaterial. The outer sleeve is optionally oriented surrounding an innersleeve and optionally is slidably positionable about an inner sleeve. Insome embodiments an outer sleeve protects an inner sleeve upon insertionof the inventive instrument and is positionally adjusted relative to theinner sleeve illustratively to a mark or other region that is optionallypositioned above the epidermis. In some embodiments the inner sleeveremains traversing the skin while the outer sleeve is positioned abovethe epidermis or penetrates to one or more desired depths or levels.

An outer sleeve is optionally positioned external to the skin or nearthe surface of the skin when the device is employed. It is appreciatedthat an outer sleeve optionally forms an upper chamber that providesuniform distribution of vacuum pressure into and throughout the innersleeve or the upper surface thereof.

An outer sleeve optionally terminates in or is integral with a collar. Acollar is optionally in fluidic connection with a conduit. In someembodiments a collar is made of a material with increased rigidityrelative to an outer sleeve.

An inventive device is optionally manufactured as a separate assembly orunitary piece so as to be associatable with a catheter prior toplacement across the skin. An inventive device is optionally formed witha slot to accept a catheter or other instrument. An instrument isoptionally slidable onto a catheter prior to inserting the catheterthrough the skin. Optionally, a catheter serves as a guide for aninventive instrument such that the instrument is slid onto a catheterfollowing catheterization into the same insertion location. Engagementof the instrument prevents agents from entering the insertion point orwill remove agents already in or under the insertion point.

In some embodiments, an inventive device is integral with a catheter orother percutaneous instrument.

An inventive complete instrument optionally includes a gasket, aconduit, a valve, and a vacuum source.

Without intending to be bound to a particular theory, a surface of aninventive device in contact with compromised skin for device insertionpromotes intercalation of fibroblasts regardless of whether the surfaceis textured, coated, or a combination thereof so as to simultaneouslypromote orthological changes in the fibroblast from circulatory form todendritic and/or stellate forms through a depth of more than one layerof fibroblast at a time and preferably more than five layers offibroblasts simultaneously anchoring to the device and more preferablymore than ten such layers of fibroblasts. Fibroblast orthologicalchanges simultaneously in more than one layer of such cells serve torapidly stabilize the percutaneous inventive device. In conjunction withthe vacuum pressure draw during the process, infection risks areminimized and an inventive device is stabilized against pullout or otherdevice motions relative to the surrounding dermal layers.

An inventive device optionally includes one or more gaskets or seals. Aseal prevents vacuum pressure from escaping to the atmosphere or fromdrawing bodily fluid into the system from the subcutaneal end of theinstrument. A gasket is optionally made from any material suitable forcreating a seal around the circumference of a catheter. A gasket isillustratively made from silicon rubber, latex, nylon, or otherpolymeric materials. A gasket is optionally connected to or integralwith an outer sleeve, an inner sleeve, a bandage, or a collar.

A conduit is optionally fluidly connected to an inner sleeve either viaa gasket or direct connection. A conduit is optionally made of anymaterial that will resist total collapse under vacuum pressures usedwith the invention.

A conduit is optionally transected by a valve. A valve is operable toengage, disengage, or adjust the vacuum pressure translated to the innersleeve. A valve is optionally mechanically or electrically controlled.Any valve or valve system known in the art is operable herein. A valveis optionally positioned at the junction between the conduit and theinstrument portions of the inventive device.

An inventive device is optionally connected to a vacuum source. A vacuumsource can be any source operable for creating negative pressure in oraround the device. A vacuum source is optionally a passive vacuum suchas a vacuum tube or bottle, or an active vacuum source illustratively amechanical pump, a syringe, or other vacuum source. A vacuum sourceoptionally applies a continuous or intermittent negative pressure. Themagnitude of the negative pressure is optionally adjustable, constant,or variable. In some embodiments an intermittent vacuum is used.Alternatively, a hydrodynamic draw agent is provided that draws fluidfrom the tissue surrounding through the sleeve via the conduit. Ahydrodynamic draw source illustratively includes a super absorbentpolymer such as sodium polyacrylate, polyacrylamide copolymer, ethylenemaleic anhydride copolymer, cross-linked carboxymethylcellulose,polyvinyl alcohol copolymers, cross-linked polyethylene oxide, andstarch grafted copolymer of polyacrylonitrile; high osmotic pressurecompositions, such as water soluble salts; and capillary flow drawagents such as dry silica, or other dry hydrophilic powders suchcellulosic material.

The inventive device optionally includes a blood or other fluiddetection system. A blood detection system is optionally a fluid sensingdevice. A fluid sensing device will optionally shut down the inventivedevice or reduce the negative pressure should too high a level of fluidpass through the conduit or otherwise into or around the inventivedevice. In some embodiments a fluid detection system will adjust thevacuum level to maintain fluid flow at a constant or variable rate.Should blood or other bodily fluid be detected at too high a rate, adetection system optionally reduces the vacuum level so as to reduce therate or adjust type of fluid flow.

An inventive instrument optionally includes a bandage. A bandageillustratively forms a seal on the surface of the skin. In someembodiments a bandage forms a chamber on the surface of the skinsurrounding the inner or outer sleeve. Although it is not absolutelynecessary, a chamber allows rapid and uniform application of a vacuumpressure around the circumference of a catheter. A bandage is optionallya polymeric material, cloth, or other material known in the art.

In some embodiments an inventive device does not penetrate the skin. Abandage optionally is associated with a gasket or is itself made ofmaterial that is operable to itself function as a gasket around acatheter. The bandage is optionally made of material with sufficientrigidity so as not to totally collapse under the negative pressure of avacuum on the epidermal side of the bandage. The bandage is optionallycircular in outer or inner shape. This circular shape is entirelyoptional. Other shapes such as triangular, square, oval, or polygonalare similarly operable.

An inventive device is optionally a bandage surrounding a catheter orother instrument wherein the bandage is in fluidic communication with avalve or conduit. A negative pressure applied on the epidermal side ofthe bandage is optionally of sufficient force to seal the outercircumference of the bandage to the epidermal layer. The presence of thevacuum itself is optionally sufficient to reduce or eliminate movementof agents into the skin of the subject at the site of the catheter.

An optional adhesive is present on the bandage or on the epidermis forcontact with the bandage. Adhesives are materials known in the art.Optionally, a bandage is integral with an instrument.

A diffuser or other porous material optionally surrounds a catheter andoptionally rests on the epidermal layer. The device is optionallymaintained in position by an adhesive that surrounds the catheterforming a seal sufficient to allow a vacuum to form around the insertionpoint. Alternatively, the vacuum itself produces a sufficient sealaround the circumference of the instrument or between the epidermis anda diffuser to both hold it one or both in place and provide sufficientpressure to draw the device onto the skin surrounding the catheter.

In some embodiments several device diameters are operable. An inventivedevice optionally has an inner diameter and an outer diameter. The innerdiameter of the device is optionally associated with the diameter of thepercutaneous instrument. A larger percutaneous instrument generally willrequire a larger inner diameter of the device. Alternatively, a singleinner diameter device is produced with removable and replaceable gasketsor seals that allow a wide range of catheter diameters or shapes to beused with the device.

In some embodiments the instrument is reusable. An inventive device isoptionally autoclavable or otherwise sterilizable.

A system for reducing or eliminating catheter related infection is alsoprovided. A system illustratively includes a plurality of inventivedevices. A plurality of devices are optionally connected to a singlevacuum source or a plurality of vacuum sources. A plurality of vacuumsources is optionally interconnected or otherwise simultaneously orindividually adjustable to increase or decrease the vacuum pressure atone or more sites of catheter insertion.

A process for reducing, preventing, reversing, treating, or eliminatinginfection at a percutaneous insertion point is also provided. Aninventive process illustratively includes applying a vacuum pressurearound the circumference of a catheter or other percutaneous instrument.The vacuum pressure causes fluid to move away from the subdermal layerspreventing infectious agents from entering the subdermal layer orpreventing additional infectious agents from entering the region duringtreatment for catheter related infection.

An inventive device is shown generally at 10 in FIG. 1 and shows asleeve 12 in fluid communication with the bore 14 of the conduit 16. Thesleeve 12 is formed of materials as detailed above with respect to theinner sleeve 12 a and is characterized by a porous matrix 18 adjacent toa perforated outer surface 20 of the conduit 16 and is co-axialtherewith. In operation, porous matrix 18 experiences strong vacuum orhydrodynamic forces 22D created by a vacuum or hydrodynamic draw source,collectively depicted at 22. The matrix 18 has a rigidity sufficient toprevent collapse under the draw pressure as an operative requirement andthereby maintain vacuum or hydrodynamic draw 22D through the matrix. Ahighly cross-linked polymeric substance, collagen, porous ceramic ormetallic substances are particularly well suited to form matrix 18. Amatrix 18 is appreciated to promote vacuum draw 22D, such large poresare sized such that both bacteria and fibroblasts 21 readily infiltratesuch pores. Without intending to be bound by a particular theory, it isbelieved that deleterious agents within the matrix 18 are actively drawninto the conduit bore 14 or if capable of biological multiplication,inhibited from doing so by the forces exerted thereon by the source 22.The distal surface 24 of the sleeve 12 has an optional nanotexture 25,as detailed above to promote fibroblast 21 pseudopod extension adherenceyet are sufficiently small to discourage bacterial colonization. It isappreciated that the distal surface 24 experiences limited draw 22D fromthe source 22. Optionally, an intermediate matrix 26 is provided betweenthe matrix 18 and the distal surface 24. The intermediate matrix 26preferably has a reduced pore size compared to matrix 18 and thisattribute alone or in combination with a reduced cross-linking densityreduces the draw forces 22D created by source 22 in this region comparedto that experienced in matrix 18. Alternatively, the matrix 26 has alike-pore size distribution relative to matrix 18, larger pore diametersrelative to matrix 18 or a graded pore dimension as a function ofthickness of intermediate matrix 26. The intermediate matrix 26 isformed of the same implant compatible material as matrix 18 or anotherimplant compatible material. To better depict the sleeve porosity, theright side of FIG. 1 only shows a single pore of intermediate matrix 26in fluid communication with pore of matrix 18. A higher degree of porecollapse associated with vacuum draw 22D through the intermediate matrix26 is not only tolerated but is believed to promote rapid stabilizationof the device 10. Accordingly, a program of source draw is optionallyprovided that varies the strength of the vacuum or osmotic pressureapplied to the matrix 18 and by extension to intermediate matrix 26 as afunction of time. The pore size in optional intermediate matrix 26 is ofa size that allows circulating fibroblasts 21 to infiltrate matrix 26and thereby initiate the healing process through formation of aninterconnected network of fibroblasts and other cells and compoundsneeded for tissue granulation. Typical cross-sectional dimensions ofpores in the matrix 26 are between 3 and 50 circulating fibroblastdiameters. It is further appreciated that the infiltration of theintermediate matrix 26 by fibroblasts operative to dimensionally extendthe device stabilization from a single layer of fibroblasts 21 seen in anon-porous surface implant to a region corresponding to the thickness ofthe intermediate matrix 26. One of skill in the art will appreciate thatthe strength of the vacuum or osmotic draw 22D from source 22 is readilyadjusted to promote infiltration into optional matrix 26 to speedstabilization. It is appreciated that the application of draw forces viasource 22 in addition to inhibiting agents and promoting fibroblastinfiltration also serves the tissue-scale function of adhering the bodytissue T surrounding the device 10 in a fixed position in contact withdevice 10 so as to form a stable interface therebetween. The resultinginterface is superior for the granulation process relative toconventional sutures or adhesive bandages. It is appreciated that thematrix 18 and the intermediate matrix 26 with a distal surface 24 thatis nanotextured are integral, or alternatively are formed as contiguousseparate layers as detailed above with respect to inner and outersleeves. A coating substance 27 optionally overcoats the surface 24,with coating substances illustratively include cellular ingressscaffolding, as will be further detailed below. The coating substancehave a tissue contacting surface 29 that is optionally nanotextured.

An inventive device is further detailed in FIG. 2 generally at 30 wherelike numerals correspond to the meaning imparted thereto with respect tothe aforementioned figure and specification text. Device 30 has acentral medical appliance 34 that is depicted as a cannula shown in thecontext of providing fluid communication between a medical appliance 34with subject vein V. The medical instrument 34 illustratively includes acatheter, cannula, pin, or wire or other percutaneous instrument withspecific versions thereof including a Steinman pin and a Kirschner wire.The device 30 is percutaneous through the epidermis, dermis, andsubcutaneous layers that are denoted at E, D, and S, respectively. Thedevice 30 has an inner sleeve 12 a that corresponds to sleeve 12detailed with respect to FIG. 1 with the exception of varying indimensionality. The inner sleeve 12 a has a porous matrix 18 in fluidcommunication with the vacuum or hydrodynamic draw source 22.Intermediate matrix 26 is optionally present intermediate between matrix18 and distal surface 24. Preferably, a coating substance 27 overliesthe distal surface 24. An outer sleeve 33 engages the medical appliance34 at a vacuum seal 36 and forms fluid communication with a vacuum orhydrodynamic draw source 22 via conduit 38. The outer sleeve 33 ofdevice 30 is shown in FIG. 2 as the outer sleeve 33 wholly envelopinginner sleeve 12 a and serves as an introducer preventing thetransmission of skin bacteria to the wound created by placement of thedevice 30 and after positioning as shown in FIG. 2, the outer sleeve 33is retracted relative to the appliance 34 and inner sleeve 12 a to aposition preferably just above epidermis E thereby allowing the source22 to draw fluid through the then exposed distal surface 24 and that ofan optional coating 27 to the surrounding tissue as well as the drawcreated source 22. It is appreciated that the relative dimensions ofattributes depicted in FIG. 2 are distorted for visual clarity.

An inventive device is depicted in FIG. 3 generally at 40 where likenumerals correspond to the meaning ascribed thereto in theaforementioned figures. The device 40 varies from that depicted in FIG.2 only in that the outer sleeve 44 is preformed to not extend the fulllinear extent of the inner sleeve 12 a and instead forms an insertionstop against the epidermis, E.

FIG. 4 is a perspective, partial cutaway view of an inventive device 50in which like numerals having the meanings ascribed thereto in theaforementioned figures. Percutaneous medical appliance 34 has a vacuumseal or gasket at 36 between a conduit 56 and a medical appliance 34.The conduit 56 is in fluid communication with an inner sleeve 12 b thatis otherwise the same as sleeves 12 and 12 a except for dimensionality.It is appreciated that inner sleeve 12 b optionally includesintermediate matrix 26 thereover, a coating substance 27, or acombination thereof. Vacuum or hydrodynamic draw 22D of the inner sleeve12 b by a conduit 56 requires vacuum draw 22D to be precluded fromregion 57 of porous inner sleeve 12 b denoted at 57. Preferential vacuumdraw 22D through region 57 relative to subdermal portions of innersleeve 12 b is accomplished through adherence of a gas-tight bandage 59to the outer surface of the epidermis E. It is appreciated that bandage59 is used as a substitute for, or in combination with, an outer sleeve54 forming a gas-tight seal with conduit 56 so as to achieve fluidcommunication between a source 22 and the subcutaneous portions of innersleeve 12 b. Optionally, a diffuser 51 constituting an open cell foammaterial or woven material is positioned intermediate between the outersurface of the epidermis E and the bandage 59 to moderate vacuum drawtherethrough.

An inventive device is shown generally at 50′ in FIG. 5, where likenumerals used therein have the meaning ascribed thereto with respect tothe aforementioned figures. The device 50′ has all the attributes ofdevice 50 save for an outer sheath 54′ having an expanded bellows-likeconstruct providing a mode of varying the linear extent of the outersleeve 54′. It is appreciated that the conduit 56 is readily constructedto be slidable relative to appliance 34 and in conjunction with outersleeve 54′.

FIG. 6 is a cross-sectional view of an inventive device, shown generallyat 60, where like numerals have the meaning ascribed thereto withrespect to the aforementioned figures. An inner sleeve 12 b has a gasketor seal 36 around the appliance 34 that contacts the outer layer ofepidermis E. A diffuser in the form of an annulus surrounds the gasketand is sealed against drawing exogenous air to the source 22 via bandage59. A vacuum draw through subject tissue, optional coating 26 and viainner sleeve 12 b, diffuser 51 through source 22 is depicted.

An inventive device is readily provided in the form of a kit with avariety of sizes of gaskets, bandages, and diffusers to provide askintight seal such that vacuum draw communication is produced betweenthe skin surrounding an inventive device through an inner sleeve to asource 22. FIGS. 7A and 7B depict an inventive device generally at 70and 80, respectively, where like numerals correspond to the meaningascribed thereto with respect to the aforementioned figures. A collarformed of a material such as silicone 72 or 82 has an annular splitallowing the collar to slide along the length of medical appliance 34and preferably remote from the surface of the epidermis E. A plasticbase 74 or 84 extends outward so that a bandage 59 is readily securedand sealed to the collar 72 or 82.

FIGS. 8A and 8B depict the percutaneous components of inventive devicewith relative dimensions of aspect exaggerated for visual clarity wherelike numerals have the meaning ascribed thereto with respect to theaforementioned figures. A flanged inner sleeve 12 c has the sameattributes as inner sleeve 12, 12 a, and 12 b and varies thereform onlyin shape. The inner sleeve 12 c is formed of materials as detailed aboveand is characterized by a large and rigid pore matrix 18 in fluidcommunication to a vacuum source 22. Sleeve 12 c has a distal surface 24that is optionally nanotextured to promote fibroblast adhesion. Thedistal surface 24, like the surfaces of any of the aforementionedsleeves 12, 12 a, or 12 b is optionally decorated with a pattern ofcontoured cell-conveying channels 83. It is appreciated that thechannels 83 can take a variety of forms. It is appreciated that anoperative device typically would have a pattern of channels 83circumferentially decorating the distal surface 24. Channel patternsoperative herein include any pattern that disfavors bacterial pocketformation. The channel 83 is formed by methods such as imprinting,embossing, molding or machining into the sleeve 12 c. Preferably, thesleeve 12 c is a nanotextured and decorated with channels 83. A channel83 according to the present invention preferably has dimensions on theorder of two to ten times the diameter of a fibroblast that isequivalent to 20 to 300 microns since a fibroblast has a diameter from10 to 15 microns. More preferably, a channel 83 has a width of between30 and 120 microns. Most preferably, channel 83 is devoid ofdiscontinuities and acute angles that disfavor cellular planarizationand adhesion. A parabolic cross section is exemplary of a channelfacilitating fibroblast growth. Preferably, the transition between thechannel 83 and the adjacent region of distal surface 24 is devoid ofdiscontinuities and acute angles that disfavor cellular planarizationand adhesion. It is appreciated that inner sleeve 12 c optionallyincludes intermediate matrix 26 thereover, a coating substance 27, or acombination thereof. The tissue contacting surface 29 of substance 27 isoptionally nanotextured. A velour 84 optionally encompasses a portion ofthe sleeve 12 c. The velour 23 is illustratively formed of DACRON®, orto the implantable polymeric material. The velour 23 is also optionallybiodegradeable.

FIG. 9 depicts an inventive device generally at 100 where like numeralscorrespond to the meaning ascribed thereto with respect to theaforementioned figures. A cap 102 is formed of a material such assilicone, a polymer or a metal and serves to keep debris from enteringthe device 100. Preferably, the cap 102 is remote from the surface ofthe epidermis E. The medical appliance 34 depicted as a catheter andvacuum or hydrodynamic draw tubing 104 pass through complementaryopenings 106 and 108, respectively formed in the cap 102. The tubing 104provides fluid communication between a vacuum or hydrodynamic drawsource 22 and an inner sleeve 12 d that has the same attributes as innersleeve 12, 12 a, 12 b, and 12 c and varies thereform only in shape. Theinner sleeve 12 d is formed of materials as detailed above and ischaracterized by a large and rigid pore matrix 18 in fluid communicationto a vacuum source 22 such that the source 22 draws tissue fluid andfibroblasts 21 into the sleeve 12 d. Sleeve 12 d has a distal surface 24that optionally nanotextured to promote fibroblast 21 adhesion. Thedistal surface 24, like the surfaces of any of the aforementionedsleeves 12, 12 a, or 12 b is optionally decorated with has a pattern ofcontoured cell-conveying channels as shown in FIGS. 8A and 8B. It isappreciated that inner sleeve 12 d optionally includes intermediatematrix 26 thereover, a coating substance 27, or a combination thereof.The coating 27 is appreciated to need not cover the entire distalsurface 24. The tissue contacting surface 29 of substance 27 isoptionally nanotextured. A flange 112 is provided to stabilize theimplanted device 100 within the subcuteanous layer S. A flange 112 isconstructed from materials and formed by methods conventional to theart. For example, those detailed in U.S. Pat. Nos. 4,634,422; 4,668,222;5,059,186; 5,120,313; 5,250,025; 5,814,058; 5,997,524; and 6,503,228.

Various modifications of the present invention, in addition to thoseshown and described herein, will be apparent to those skilled in the artof the above description. Such modifications are also intended to fallwithin the scope of the appended claims.

Patents and publications mentioned in the specification are indicativeof the levels of those skilled in the art to which the inventionpertains. These patents and publications are incorporated herein byreference to the same extent as if each individual application orpublication was specifically and individually incorporated herein byreference.

The foregoing description is illustrative of particular embodiments ofthe invention, but is not meant to be a limitation upon the practicethereof. The following claims, including all equivalents thereof, areintended to define the scope of the invention.

The invention claimed is:
 1. A device for reducing agent penetration atan insertion site in subject tissue comprising: a medical appliancehaving an outer surface, said medical appliance configured to extendfrom outside the subject tissue to beneath the subject tissue, and wheresaid medical appliance is one of: a peripherally inserted centralcatheter (PICC), a cannula, a catheter, a Steinman pin, or a Kirschnerwire; a conduit with an open proximal end and an open distal end, saidconduit forming a seal with the outer surface of said medical appliance;a porous inner sleeve fluidly surrounding the outer surface of saidmedical appliance and connected to said conduit, said porous innersleeve configured to extend extending from above an epidermis layer ofthe subject tissue in the insertion site, and through the epidermislayer to a subcutaneous layer of the subject tissue; an outer sleevethat is textured with pores, ridges, depressions, or indentations atleast partially surrounding said porous inner sleeve, said porous innersleeve and said outer sleeve being coaxial with said medical appliance;a vacuum source of a mechanical pump fluidly connected to the openproximal end of said conduit drawing vacuum against the subject tissueat the insertion site through said outer sleeve and said porous innersleeve through said conduit to draw fibroblasts into and onto said outersleeve; and an intermediate matrix having a reduced pore size comparedto said porous inner sleeve, said intermediate matrix between saidporous inner sleeve and said outer sleeve, said intermediate matrixexperiences vacuum forces created by the vacuum source in communicationwith said intermediate matrix, said intermediate matrix having arigidity sufficient to prevent collapse.
 2. The device of claim 1wherein said porous inner sleeve or said outer sleeve further comprisesa coating substance.
 3. The device of claim 1 wherein said porous innersleeve or said outer sleeve further comprises a coating compound, andsaid coating compound is a growth factor, extracellular matrix factors,fibroblast receptors, fibronectin, laminectin, RGD factor,dexamethasone, or combinations thereof.
 4. The device of claim 1 furthercomprising a fluid, biological, or chemical-sensing device.
 5. Thedevice of claim 1 further comprising a gas-tight bandage.
 6. The deviceof claim 5 further comprising a diffuser configured to be positionedintermediate between an outer surface of the epidermis and said bandage.7. The device of claim 1 wherein said outer sleeve is fluidly connectedto said conduit through said porous inner sleeve, where said outersleeve movably surrounds said porous inner sleeve, and said porous innersleeve or said outer sleeve is treated or shaped to encourage fibroblastattachment.
 8. A device for reducing agent penetration at an insertionsite comprising: a medical appliance having an outer surface, saidmedical appliance configured to extend from outside the insertion siteto beneath a subject tissue, and where said medical appliance is one of:a peripherally inserted central catheter (PICC), a cannula, a catheter,a Steinman pin, or a Kirschner wire; a conduit having a bore and anouter conduit surface, said conduit with an open proximal end and anopen distal end, said conduit forming a seal with the outer surface ofsaid medical appliance; a sleeve in fluid communication with the outerconduit surface of said conduit, said sleeve formed of a materialcharacterized by a pore matrix through which vacuum draw is achieved,and where said sleeve and said conduit are coaxial with said medicalappliance; and an intermediate matrix between the pore matrix and theouter conduit surface, the intermediate matrix having a reduced poresize compared to the pore matrix, said intermediate matrix experiencesvacuum forces created by a vacuum source a mechanical pump incommunication with said intermediate matrix, said intermediate matrixhaving a rigidity sufficient to prevent collapse under a draw pressure,and thereby maintain vacuum forces through the intermediate matrix. 9.The device of claim 8 wherein the pore matrix is a contiguous piecejoined to the intermediate matrix to form said sleeve.
 10. The device ofclaim 8 wherein the pore matrix is integral with the intermediate matrixto form a monolithic sleeve.
 11. The device of claim 8 wherein theintermediate matrix has a pore size of between 3 and 50 migratoryfibroblast diameters.
 12. The device of claim 8 wherein said sleeveincludes a scaffold.
 13. The device of claim 8 wherein said sleevefurther comprises a coating compound, said coating compound is growthfactor, extracellular matrix factors, fibroblast receptors, fibronectin,laminectin, RGD factor, dexamethasone, or combinations thereof.
 14. Thedevice of claim 8 wherein said sleeve surrounds said medical appliance.15. The device claim 8 wherein the pore matrix and the intermediatematrix are inhomogeneous with respect to at least one property ofmechanical, geometrical, cross-linking, or biological properties. 16.The device of claim 8 wherein the outer conduit surface is nanotextured.